Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse, France.
Laboratory of Animal Pathology, Universidade Estadual de Londrina, Londrina, Brazil.
Environ Int. 2019 Nov;132:105082. doi: 10.1016/j.envint.2019.105082. Epub 2019 Aug 7.
Deoxynivalenol (DON), one of the most widespread mycotoxins in Europe, and cadmium (Cd), a widespread environmental pollutant, are common food contaminants. They exert adverse effects on different organs including kidney, liver, and intestine. The intestine is a common target of DON and Cd when they are ingested. Most studies have focused on their individual effects whereas their combined toxicity has rarely been studied. The aim of this study was thus to evaluate their individual and combined effects on the intestinal barrier function in vitro and in vivo. In vitro, Caco-2 cells were treated with increasing concentrations of DON and Cd (1-30 μM). In vivo, Wistar rats were used as controls or exposed to DON contaminated feed (8.2 mg/kg feed), Cd-contaminated water (5 mg/l) or both for four weeks. In Caco-2 cells, DON, Cd and the DON+Cd mixture reduced transepithelial electrical resistance (TEER) and increased paracellular permeability in a dose-dependent manner. Impairment of the barrier function was associated with a decrease in the amount of E-cadherin and occludin after exposure to the two contaminants alone or combined. A decrease in E-cadherin expression was observed in rats exposed to the two contaminants alone or combined, whereas occludin expression only decreased in animals exposed to DON and DON+Cd. Jejunal crypt depth was reduced in rats exposed to DON or Cd, whereas villi height was not affected. In vitro and in vivo results showed that the effects of exposure to combined DON and Cd on the intestinal barrier function in the jejunum of Wistar rats and in the colorectal cancer cell line (Caco-2) was similar to the effects of each individual contaminant. This suggests that regulations for each individual contaminant are sufficiently protective for consumers.
脱氧雪腐镰刀菌烯醇（DON）是欧洲分布最广泛的霉菌毒素之一，镉（Cd）是一种广泛存在的环境污染物，它们是常见的食品污染物。它们对包括肾脏、肝脏和肠道在内的不同器官都有不良影响。当它们被摄入时，肠道是 DON 和 Cd 的常见靶器官。大多数研究都集中在它们的单独作用上，而它们的联合毒性很少被研究。因此，本研究旨在评估它们在体外和体内对肠道屏障功能的单独和联合作用。在体外，用递增浓度的 DON 和 Cd（1-30 μM）处理 Caco-2 细胞。在体内，Wistar 大鼠被用作对照或暴露于 DON 污染的饲料（8.2mg/kg 饲料）、Cd 污染的水（5mg/l）或两者混合的饲料中 4 周。在 Caco-2 细胞中，DON、Cd 和 DON+Cd 混合物以剂量依赖的方式降低跨上皮电阻（TEER）并增加细胞旁通透性。暴露于两种污染物单独或联合后，屏障功能的损害与 E-钙黏蛋白和闭合蛋白的量减少有关。在单独或联合暴露于两种污染物的大鼠中观察到 E-钙黏蛋白表达减少，而仅在暴露于 DON 和 DON+Cd 的动物中观察到闭合蛋白表达减少。暴露于 DON 或 Cd 的大鼠空肠隐窝深度降低，而绒毛高度不受影响。体内和体外结果表明，暴露于 DON 和 Cd 混合物对 Wistar 大鼠空肠和结直肠癌细胞系（Caco-2）肠道屏障功能的影响与每种单独污染物的影响相似。这表明，针对每种单独污染物的法规对消费者具有足够的保护作用。
